The overall goal of this proposal remains unchanged and is to investigate the effect of pregnancy on response to highly active antiretroviral therapy (HAART) among HIV-i- women in treatment in Johannesburg, South Africa. In addition, we will continue developing the advanced quantitative epidemiologic methods described in the training component ofthe K99 portion of this grant. Prevalence of HIV among pregnant women in South Africa is substantially higher than that among other adults. Despite extensive study of interventions for the prevention of mother to child transmission of HIV, and response to antiretroviral therapy during and after such interventions, little is known about the effect of pregnancy itself on responses to and retention in therapy. Fully understanding the effect of pregnancy on maternal responses to HAART is essential to providing good clinical care to H1V+ women in Africa and elsewhere. To address these questions, this work proposes to examine the effect of pregnancy on immunologic responses to HAART, clinical (AIDS/death) responses to HAART, and to adherence to HAART and retention in care. Because it is impossible (and highly unethical) to randomize the exposure of pregnancy, this study will rely on high quality clinical data collected in the Themba Lethu Clinic in Johannesburg, South Africa, an urban antiretroviral therapy clinic associated with the Clinical HIV Research Unit at the University ofthe Witwatersrand. The Principal Investigator of the proposed work, Dr. Daniel Westreich, has a strong track record in producing high quality research in collaboration with investigators and clinicians at the Clinic. The analysis of these data will require the use of structural models, an advanced body of epidemiologic methods.